With an ageing population putting ever increasing demands on the musculoskeletal system there is a growing need for the development of regenerative medical strategies to provide for the healthcare needs of the future. With increasing numbers of joint arthroplasty occurring in younger and younger patients there is likely to be a growing need for therapeutic strategies to replace lost bone stock in the coming decades This thesis aims to explore strategies to enhance the biological and mechanical properties of impaction bone grafting and the effects of skeletal stem cell (SSC) concentration. In order for SSC to be effective in replacing new bone stock new strategies looking to enhance osteogenic differentiation have been examined. Section I: An in vitro Impaction Bone Graft (lBG) model of SSC seeded onto human allograft was used to study the biomechanical effects of altering SSC concentration. The use of concentrated SSC was then used in the treatment of patients with avascular necrosis (AVN) of the femoral head and fracture non union with parallel in vitro analysis of the samples. Section 11: In vitro and murine in vivo analysis of the biomechanical effects of type 1 Collagen and Hydroxyapatite nanoparticles primarily looking at differences in shear strength and osteogenic differentiation compared to plain allograft and basal cultured SSC. Section Ill: An in vitro acetabular model was used to study the effect of vibration IBG compared to standard techniques in revision hip surgery. The graft compaction, force of impaction, fracture risk and rate of subsidence post cyclical loading was assessed. This thesis has demonstrated in vitro and in vivo strategies that are clinically translatable and have demonstrated that: • Skeletal Stem Cell concentration plays a pivotal role in the biomechanical enhancement of Impacted bone graft (IBG) • Translation of these strategies into the successful treatment of fracture non union and Avascular necrosis of the hip. • Type 1 Collagen and Hydroxyapatite nanoparticles both enhance the osteogenic differentiation and shear strength of the IBG / SSC construct • Vibration impaction bone grafting is a novel technique that significantly reduces the intraoperative risk of acetabular fracture or catastrophic subsidence This thesis has demonstrated novel techniques for the biomechanical enhancement of I BG with most techniques being readily transferable to clinical practice with the potential to form part of a surgeon's armament for regenerative medical techniques of the future.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:588807 |
| Date | January 2012 |
| Creators | Jones, Andrew |
| Contributors | Oreffo, Richard ; Dunlop, Douglas |
| Publisher | University of Southampton |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://eprints.soton.ac.uk/361469/ |
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